The term “stem cells” is a generic name for cells that can differentiate into diverse specialized cell types and are found undifferentiated in embryos, fetuses, and adults. Among stem cells, blood adult stem cells which are derived from bone marrow refer to the stem cells with pluripotency that can differentiate into all kind of cells constituting organs and blood of human body.
Bone marrow-derived stem cells are considered as the ultimate therapeutic means for blood cancer, lymphoma, and bone marrow failure, but there is a difficulty in harvesting the bone marrow. To surmount this difficulty, a G-CSF injection has recently been used to mobilize stem cells from bone marrow into blood. However, G-CSF itself has the potential to cause side effects. On the other hand, stem cells are also derived from umbilical cord blood and deposited in a frozen form with cord blood banks. Umbilical cord blood-derived stem cells are actively studied, but quantitatively limited. Under these situations, it is very important to develop a method of obtaining a sufficient number of blood adult stem cells.
Conventional methods of expanding blood adult stem cells in vitro are, for the most part, directed towards the establishment of bone marrow-mimic environments with artificial substances, and are, in part, successful (Peerani R, Zandstra P W. Enabling stem cell therapies through synthetic stem cell-niche engineering. Journal of Clinical Investigation. 2010; 120: 60-70.). However, because the bone marrow, the source of blood adult stem cells, provides contacts with various supporting-cells and contains cytokines released from the cells and an extracellular matrix, it is difficult to establish a mimic environment sufficient to expand blood adult stem cells using artificial substances.
Meanwhile, some research and development groups in the study of stem cell derived from adult tissue have succeeded in developing techniques of expanding number of stem cells or maintaining the pluripotency of stem cells derived from heart or brain tissues by spheroid culture systems (Caldwell M A, He X, Wilkie N, et al. Growth factors regulate the survival and fate of cells derived from human neurospheres. Nat Biotech. 2001; 19: 475-479; and Messina E, De Angelis L, Frati G, et al. Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ Res. 2004; 95: 911-921.).
Leading to the present invention, intensive and thorough research into the in vitro expansion of blood adult stem cells, aiming to overcome the problems encountered in the prior art, resulted in the development of human blood born-hematospheres culture to simply expand blood adult stem cells without losing their pluripotency.